title: Hematological and cardiometabolic safety of clozapine in the treatment of very early onset schizophrenia: a retrospective chart review.
abstract: OBJECTIVE
  There are very few studies in the literature regarding clozapine use in children <13 years of age. In this retrospective chart review, we compared the safety of clozapine--as determined by hematological and cardiometabolic changes - to that of non-clozapine antipsychotics used in the treatment of childhood-onset schizophrenia (COS).
  
  
  METHODS
  The clozapine treatment group (CTG) consisted of 17 COS patients (mean age 10.4 ± 2 years) who were hospitalized in a psychiatric ward between the years 2005 and 2012. The control group consisted of 19 COS patients (mean age 10.1 ± 1.4 years) who were hospitalized in the same ward during the same time period, and were treated with non-clozapine antipsychotics. A retrospective chart review was conducted. Hematological (white blood cells, absolute neutrophil count [ANC], red blood cells, platelets), metabolic (aspartate transaminase, alanine transaminase, triglycerides, total cholesterol, bilirubin) and cardiac (heart rate) values were extracted from the medical charts.
  
  
  RESULTS
  The average follow-up periods for the CTG and the control group were 332.9 ± 200.5 days and 291.7 ± 157 days, respectively. In the CTG, moderate neutropenia (ANC<1500/mm(3)) and mild neutropenia (1500/mm(3)<ANC<2000/mm(3)) were observed in two children (12%) and one child (6%), respectively. The neutropenia was transient in all cases. Treatment with clozapine was permanently discontinued only in one child (6%). There were no cases of agranulocytosis or severe infection in the CTG. In the control group, two children (11%) showed hematological abnormalities. Hyperlipidemia was observed in one child (6%) in the CTG at release from the hospital. Significantly more children (47%) in the CTG had tachycardia (heart rate>100 beats per minute) at release from the hospital, compared with only one child (5%) in the control group (p=0.006).
  
  
  CONCLUSIONS
  It appears that clozapine use in very early onset schizophrenia is safe. Although hematological adverse effects did occur in our study, the rates were not much higher than those seen in the control group. We found that the hematological abnormalities in the CTG were mostly transient, and that treatment with clozapine can be safely continued or renewed.
authors.affiliation: 1 Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, Israel .
authors.forename: Yael
authors.initials: Y
authors.lastname: Midbari
authors.forename: Tanya
authors.initials: T
authors.lastname: Ebert
authors.forename: Ira
authors.initials: I
authors.lastname: Kosov
authors.forename: Moshe
authors.initials: M
authors.lastname: Kotler
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
authors.forename: Anca
authors.initials: A
authors.lastname: Ram
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D016022:Case-Control Studies; D002648:Child; D003024:Clozapine / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D006402:Hematologic Diseases / Q000139:chemically induced* / Q000150:complications; D006801:Humans; D008499:Medical Records; D012189:Retrospective Studies; D012559:Schizophrenia / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine